Part 1: Background: Some patients with outlet obstruction to defecation have delayed left colonic transit and reduced postprandial motility for unknown reasons (Am J Gastro 1996;91:2532-8). We hypothesized that phasic rectal distention is associated with colonic relaxation presumably due to a viscero-visceral reflex. Our aims were to compare the effects of rectal and colonic distention on colonic and rectal tone respectively. Methods: In 26 healthy volunteers, we placed barostat balloons in the cleansed descending colon (DC, 10 cm long) and the rectum (R, 8 cm long, 5 cm from the anal verge). After a 30 minute equilibration period, the intraballoon pressure was set to operating pressure (OP), i.e. 2 mmHg above the pressure at which respiratory excursions were regularly recorded as changes in barostat volume. The OP was maintained for 30 minutes. Thereafter we applied phasic distentions 8, 16 and 32 mmHg above OP for 1 minute, with a 1 minute interstimulus interval. The order of distentions and the order of distending the colon or rectum were randomized with a 20 minute equilibration period between series of colonic and rectal distentions. The barostat balloon volume was averaged over 30 seconds prior to and over a 30 second interval beginning 20 seconds after the onset of each distention. Part 2: Background: The acetylcholinesterase inhibitor neostigmine (Neo) enhances colonic motor activity and reduces colonic distention in Ogilvie's syndrome. The effects of bethanechol (Beth), a cholinergic agonist on the colon are unclear. Our aims were to compare the effects of Neo and Beth on colonic and rectal tone and phasic activity, compliance and sensation in a parallel group study. Methods: 30 volunteers were randomized to receive one agent, either Neo (0.25 mg, 0.75 mg, or 1.5 mg i.v.) or Beth (2.5 mg, 5 mg or 10 mg s.q). A barostat-manometric assembly was positioned with a 10cm balloon in the cleansed descending colon (DC), 4 manometric sensors in the DC and 2 in the sigmoid (SC); a separate rectal (r) balloon was placed 5cm from the anal verge. We measured fasting colonic tone, phasic activity, compliance (2-mmHg pressure increments from 0-36 mmHg), and sensation before and after drug administration. Sensation was assessed with a 100-mm VAS scale for gas (G), urgency (U) and pain (P) during phasic balloon distentions (1 min duration; 8,16 and 32mmHg above operating pressure (OP) in random order). Sensation scores averaged over all distention pressures. The compliance curves were fit using a power-exponential model. Phasic deflections were summarized as motility index (MI)/Hr = ln {(# of contractions*sum of heights) + 1}separately for sensors 1-6..